Chronic low back pain (CLBP) afflicts up to 50 million US adults and is a primary cause of disability. Currently, opioid analgesics are a cornerstone of pain management, and are among the most common medications prescribed by physicians for CLBP. Despite their potential benefits, major concerns have been raised regarding opioids due to their potential iatrogenic consequences, such as the development of opioid-induced hyperalgesia (OIH) and prescription opioid misuse (POM), both of which have the potential to impair treatment benefits. It is clear that not all patients taking long-term opioids will experiene these maladaptive effects. Our preliminary data indicate that specific subgroups of pain patients might be more prone to developing OIH, as well as deleterious shifts in central nervous system (CNS) pain-modulatory processes. Furthermore, our preliminary data suggest that OIH and opioid-induced changes in pain modulation might increase patients' propensity to misuse opioids. Given the current opioid prescribing rates in the U.S., there is an urgent need to better understand effects of opioids on CNS pain processing and, in turn, the effects of those sensory changes on risk for opioid misuse or addiction. In this study, we propose to conduct a 4-month randomized, controlled trial of oral opioids among patients with CLBP. In this trial, each participant will undergo quantitative sensory testing (QST) at baseline, before being randomized to receive either extended-release oral morphine or matched placebo. Patients will then undergo repeat QST at 1, 2, 3, and 4 months. At each of these follow-up time points, we will assess changes in pain sensitivity and modulation, and prescription opioid misuse. Treatment efficacy will be assessed using daily electronic dairy entries We hypothesize that an identifiable subgroup of patients, characterized by high levels of negative affect and pain catastrophizing, will be at the greatest risk for experiencing maladaptive opioid-induced changes in pain sensitivity (i.e., OIH) and pain modulation, as well as an increased likelihood of prescription opioid misuse. Collectively, there is a very strong animal literature on OIH (which seems to be a highly robust phenomenon in rats), but there is currently a paucity of prospective human data. We hope that findings from this research would be novel, timely, and would have direct implications for the field of opioid pain management. Identifying subgroups of patients who are at elevated risk for OIH and POM should facilitate more effective tailoring of treatment regimens to individual patients, and aid in reducing the potentially severe iatrogenic impacts of long-term opioid therapy in patients with chronic pain.